Impact of a varied set of stimuli on a suite of immunological parameters within peripheral blood mononuclear cells:toward a non-animal approach for assessing immune modulation by materials intended for human use

Introduction: In toxicology, steps are being taken towards more mechanism-focused and human relevant approaches to risk assessment, requiring new approaches and methods. Additionally, there is increasing emphasis by regulators on risk assessment of immunotoxicity.Methods: Here we present data from a peripheral blood mononuclear cell (PBMC) system whereby a varied set of stimuli, including those against the TCR and Toll-like receptors, enable readouts of cytokine and prostaglandin E2 (PGE2) production with monocyte, T cell and B cell viability, proliferation, and associated activation markers. In addition to results on the impact of the stimuli used, initial profiling data for a case study chemical, curcumin, is presented, illustrating how the system can be used to generate information on the impact of exogenous materials on three major constituent immune cell subsets for use in risk assessment and to direct follow-on studies.Results: The different stimuli drove distinct responses, not only in relation to the “quantity” of the response but also the “quality”. Curcumin had a limited impact on the B cell parameters measured, with the stimuli used, and it was noted that in contrast to T cells where there was either no impact or a reduction in viability and proliferation with increasing concentration, for B cells there was a small but significant increase in both measurements at curcumin concentrations below 20 µM. Similarly, whilst expression of activation markers by T cells was reduced by the highest concentration of curcumin, they were increased in B cells. Curcumin only impacted the viability of stimulated monocytes at the highest concentration and had differential impact on different activation markers. Levels of all cytokines and PGE2 were reduced at higher concentrations.Discussion: Although the platform has certain limitations, it nevertheless enables assessment of healthy baseline monocyte, T-, and B-cell responses, and scrutiny of the impact of different stimuli to detect potential immune suppression or enhancement from exogenous materials. In the case of curcumin, a pattern of responses indicative of immune suppressive / anti-inflammatory effects was detected. It is an accessible, highly modifiable system that can be used to screen materials and guide further studies, providing a holistic, integrated picture of effects

Design and Feasibility Analysis of a Smartphone‐Based Digital Cognitive Assessment Study in the Framingham Heart Study

Background Smartphone‐based digital technology is increasingly being recognized as a cost‐effective, scalable, and noninvasive method of collecting longitudinal cognitive and behavioral data. Accordingly, a state‐of‐the‐art 3‐year longitudinal project focused on collecting multimodal digital data for early detection of cognitive impairment was developed. Methods and Results A smartphone application collected 2 modalities of cognitive data, digital voice and screen‐based behaviors, from the FHS (Framingham Heart Study) multigenerational Generation 2 (Gen 2) and Generation 3 (Gen 3) cohorts. To understand the feasibility of conducting a smartphone‐based study, participants completed a series of questions about their smartphone and app use, as well as sensory and environmental factors that they encountered while completing the tasks on the app. Baseline data collected to date were from 537 participants (mean age=66.6 years, SD=7.0; 58.47% female). Across the younger participants from the Gen 3 cohort (n=455; mean age=60.8 years, SD=8.2; 59.12% female) and older participants from the Gen 2 cohort (n=82; mean age=74.2 years, SD=5.8; 54.88% female), an average of 76% participants agreed or strongly agreed that they felt confident about using the app, 77% on average agreed or strongly agreed that they were able to use the app on their own, and 81% on average rated the app as easy to use. Conclusions Based on participant ratings, the study findings are promising. At baseline, the majority of participants are able to complete the app‐related tasks, follow the instructions, and encounter minimal barriers to completing the tasks independently. These data provide evidence that designing and collecting smartphone application data in an unsupervised, remote, and naturalistic setting in a large, community‐based population is feasible